Patent GB-660582-A (GB)
Title: Antibiotics
Filed: 1948-07-14
Abstract: Salt-like compounds of basic antibiotics of the streptomycin type (i.e. streptomycin itself or antibiotically-active basic compounds which likewise form water-soluble salts with acids such as sulphuric acid and water-insoluble salts with organic-base-precipitating agents, e.g. dihydrostreptomycin or streptothricin) with surface-active agents of the organically-substituted polybasic-inorganic-acid type are manufactured by contacting an aqueous solution of the antibiotic (or a salt thereof) with the surface-active agent and with a substantially water-immiscible organic solvent for soaps (e.g. in the order stated or simultaneously), and separating the organic solvent phase from the aqueous phase (preferably after adjusting the pH of the latter to between 3 and 4 when the antibiotic is streptomycin).  The salt-like compound may be isolated from the organic solvent phase (e.g. by evaporating the solvent in vacuo, or, in suitable cases, by freeze-drying), and may be directly used for therapeutic purposes or converted into a water-soluble salt, or the latter may be obtained directly from the organic solvent solution by treating it (preferably after washing with water) with an aqueous water-soluble relatively strong acid (e.g. sulphuric, hydrochloric, phosphoric, oxalic, citric, sulphamic or nitric acid) and recovering the aqueous phase, which may then be dried, preferably freeze-dried.  Suitable surface-active agents are especially compounds of the general formula R-O-X-O-Y, wherein R represents the residue of a substantially water-immiscible organic hydroxy compound, -O-X-O represents the bivalent acid residue of a water-soluble polybasic inorganic acid (e.g. sulphuric or phosphoric acid) and Y represents hydrogen or a cation forming a water-soluble salt with the anion R-O-X-O- (e.g. mono-higher-aliphatic esters of sulphuric acid or water-soluble salts thereof), or also aromatic sulphonic acids, sulphonated oils or sulphonated higher fatty acid derivatives, or water-soluble salts thereof, all these types of compounds being exemplified.  As organic solvents for soaps (which term includes invert soaps) may be used hydrocarbons (e.g. benzene or toluene), halogenated hydrocarbons (e.g. ethylene dichloride, chloroform or carbon tetrachloride), aliphatic ethers (e.g. di-n-butyl or diethyl ether), aliphatic ketones (e.g. methyl isobutyl ketone), aliphatic alcohol esters of lower fatty acids (e.g. amyl or methylisobutylcarbinyl acetate), or preferably aliphatic alcohols (e.g. 1-pentanol, n- or sec.-butanol, methylisobutylcarbinol, methylaurylcarbinol, methylisopropylcarbinol, isobutylcarbinol, 2-ethylhexanol or especially refined fermentation amyl alcohol). The process is applicable to the recovery of streptomycin from a primary streptomycin-containing liquid (i.e. fermented culture medium from which the solids have been removed, or the product obtained by treating such medium or the separated solids with acid, followed by neutralization), or to the purification of basic antibiotics of the streptomycin type (e.g. streptomycin as present in a primary streptomycin-containing liquid or in a solution obtained therefrom by adsorbing the streptomycin on activated charcoal and eluting it with an aqueous water-soluble mineral acid). An antibiotic so purified may be further purified by repetition of the process, or may be preliminarily or further purified by other methods, of which several are specified. Examples illustrate the various features of the invention, the following surface-active agents being employed: sulphated oleyl alcohol, turkey red oil, poly-alkylated monosodium benzenesulphonates, and the compounds of the formul  <FORM:0660582/IV (b)/1> and <FORM:0660582/IV (b)/2> Specification 660,583 is referred to.